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NCI RAS Initiative Update
Ras Initiative Update Frank McCormick and Levi Garraway DEPARTMENT OF HEALTH AND HUMAN SERVICES • National Institutes of Health • National Cancer Institute The Frederick National Laboratory is a Federally Funded Research and Development Center operated by Leidos Biomedical Research, Inc., for the National Cancer Institute RAS Initiative Accomplishments: Evaluating Ras dependency 2 SiREN assay for Ras dependency SiREN assay for Ras dependency 70% KD siEGFP 0-10% KD 50% KD 100% KD SiREN assay for Ras dependency RAS Initiative Accomplishments: Biophysical and structural analysis 7 Ras proteins 1 -166 167-185,6 Raf, PI 3’ kinase RalGDS, GAPs Raf, PI 3’ kinase RalGDS, GAPs Raf, PI 3’ kinase RalGDS, GAPs Raf, PI 3’ kinase RalGDS, GAPs Palmitoyl Farnesyl Fully processed KRAS4b A. Gorfe, U-Texas Houston Engineering baculovirus for improved production of processed KRAS • recombineering used to insert FNTA/FNTB genes into the baculovirus genome • eliminated issues with coinfection of multiple viruses • maltose-binding protein (MBP) fusion for greater yield and solubility • Trichoplusia ni (Hi5) insect cells for increased yield Carissa Grose, Dom Esposito, Bill Gillette Processed KRAS4b characterization • Extensive protein characterization – Purified to homogeneity; yield >7mg/L – Intact mass – Predominantly monomeric – Secondary structure equivalent to non-processed KRAS4b KRAS4b- FME – Lower thermal stability Intact mass analysis Analytical ultracentrifugation Secondary structure by CD 2.14 S 25.7 kDa 10 Bill Gillette, Zhaojing Meng, Shelley Perkins, -
Miriam Molina Arcas
CV Miriam Molina Arcas Miriam Molina Arcas Principal Laboratory Research Scientist The Francis Crick Institute 1 Midland Road, NW1 1AT London +442037963313 [email protected] EDUCATION 1999-2005 PhD in Biomedicine, University of Barcelona, Spain Role of equilibrative nucleoside transporters in the sensitivity to antineoplasic drugs. Supervisors: Prof. Marçal Pastor-Anglada and Dr. F. Javier Casado 1994-1999 BSc Biochemistry, University of Barcelona, Spain RESEARCH AND PROFESSIONAL EXPERIENCE June 2016- present Senior Laboratory Research Scientist, Oncogene Biology Laboratory, The Francis Crick Institute. Prof. Julian Downward. Studied combination approaches that improve the efficacy of KRAS inhibitors and reduce resistance mechanisms. March 2015- May 2016 Postdoctoral Fellow, Lung Cancer Team, Institute of Cancer Research. Prof. Julian Downward. Designed and optimized a whole-genome shRNA screen to identify synthetic lethal interactions with MEK and IGF1R inhibitors. Sep 2008- Feb 2015 Postdoctoral Fellow, Signal Transduction Laboratory, Cancer Research UK- London Research Institute. Prof. Julian Downward Using RNA interfering and drug screens, identified new therapeutic strategies to treat tumours harbouring KRAS mutations 2006- Aug 2008 Postdoctoral Fellow, University of Barcelona, Spain Prof. Marçal Pastor-Anglada Studied the role of membrane transporters in nucleoside-derived drug response in cancer and HIV. TEACHING AND MENTORING EXPERIENCE 2018-2021 Honorary Research Associate in the School of Life & Medical Sciences, University College London, part of the Certificate in Core Teaching Practices. 2007-2008 Part-time lecturer of Biochemistry and Molecular Biology (University of Barcelona). 180h of theory and practical lessons. 2003-2005 Teaching assistant of Biochemistry and Molecular Biology (University of Barcelona). 60h of practical lessons. September 2019 Co-supervisor of MSc Experimental Pharmacology and Therapeutics Research of Pablo Romero Clavijo at the University College London. -
(Sozial)Leben in Graz & Oberschützen
(SOZIAL)LEBEN IN GRAZ & OBERSCHÜTZEN 1 Wissenswertes über ÖSTERREICH Du möchtest in Österreich studieren? Wir haben dir hier ein paar wichtige Fakten zusammengestellt, damit du dich schnell zurechtfindest! FACTS ÜBER ÖSTERREICH Hauptstadt: Einwohner_innenzahl: Wien ca. 8,8 Mio. Größe: Währung: 83.858 km² Euro (€ 1 = 100 Cent) Bundesländer: Nachbarländer: Burgenland, Kärnten, Niederösterreich, Deutschland, Italien, Liechtenstein, Schweiz, Oberösterreich, Salzburg, Steiermark, Tirol, Slowakei, Slowenien, Tschechien, Ungarn Vorarlberg, Wien Klima: Zeitzone: Gemäßigtes Klima: milde Sommer mit Mitteleuropäische Zeitzone (MEZ), UTC + 1, Hitzeperioden (bis zu +30 °C), kalte und nasse 2x/Jahr (Ende März/Ende Oktober): Winter mit Schnee (bis zu -15 °C) Zeitumstellung Berühmte österreichische Künstler_innen: Fauna und Flora: Wolfgang Amadeus Mozart, Johann Strauss, Keine Kängurus , dafür ist aber die Elfriede Jelinek, Joseph Haydn, Franz Schubert, mitteleuropäische Tierwelt vorzufinden: z.B. Franz Liszt, Anton Bruckner, Egon Schiele, Gustav Rehe, Hirsche, Hasen, Fasanen, Füchse, Dachse, Klimt, Oskar Kokoschka, Gustav Mahler, Peter Marder, Rebhühner u.v.m. Handke, Thomas Bernhard, Helmut Qualtinger, Außerdem gibt es viele Laubwälder (Eichen, u.v.m. Buchen) bzw. Mischwälder (Buchen, Fichten) in höheren Regionen Fichten, Lärchen und Zirben. Traditionelle österreichische Küche: Sportliche Aktivitäten: z.B. Tafelspitz, Wiener Schnitzel, Steirisches z.B. Wintersport: Skifahren, Langlaufen, Backhendl, Gulasch, Sachertorte, Eislaufen, Sommersport: Radfahren, -
Unveiling New Disease, Pathway, and Gene Associations Via Multi-Scale Neural Networks
Unveiling new disease, pathway, and gene associations via multi-scale neural networks Thomas Gaudelet 1, No¨elMalod-Dognin 2, Jon S´anchez-Valle 2, Vera Pancaldi 2,3,4, Alfonso Valencia 2,5,6 and NataˇsaPrˇzulj 2,5,∗ 1 Department of Computer Science, University College London, London, WC1E 6BT 2 Department of Life Sciences, Barcelona Supercomputing Center (BSC), Barcelona, 08034 Spain 3 Centre de Recherches en Canc´erologiede Toulouse (CRCT), UMR1037 Inserm, ERL5294 CNRS, 31037 Toulouse, France 4 University Paul Sabatier III, Toulouse, France 5 ICREA, Pg. Llu´ısCompanys 23, 08010 Barcelona, Spain 6 Coordination Node. Spanish National Bioinformatics Institute, ELIXIR-Spain (INB, ELIXIR-ES), Spain ∗ [email protected]. Abstract Diseases involve complex modifications to the cellular machinery. The gene expression profile of the affected cells contains characteristic patterns linked to a disease. Hence, new biological knowledge about a disease can be extracted from these profiles, improving our ability to diagnose and assess disease risks. This knowledge can be used for drug re-purposing, or by physicians to evaluate a patient's condition and co-morbidity risk. Here, we consider differential gene expressions obtained by microarray technology for patients diagnosed with various diseases. Based on these data and cellular multi-scale organization, we aim at uncovering disease{disease, disease{gene and disease{pathway associations. We propose a neural network with structure based on the multi- scale organization of proteins in a cell into biological pathways. We show that this model is able to correctly predict the diagnosis for the majority of patients. Through the analysis of the trained model, we predict disease{ disease, disease{pathway, and disease{gene associations and validate the predictions by comparisons to known interactions and literature search, proposing putative explanations for the predictions. -
Fellows Opted out of the Mentoring Programme As of 21 July 2020 1 of 3 Professor Chris Abell FRS Fmedsci Professor Philip Jones
Fellows opted out of the Mentoring programme as of 21 July 2020 Professor Chris Abell FRS FMedSci Professor Philip Jones FMedSci Professor David Adams FMedSci Professor Roger Jones FMedSci Professor Judith Allen FRSE FMedSci Professor Kamlesh Khunti FMedSci Professor Thomas Kirkwood CBE Professor Desmond Archer OBE FMedSci FMedSci Professor Louise Arseneault FMedSci Professor Robb Krumlauf FMedSci Professor Charalambos Kyriacou Professor Michael Arthur FMedSci FMedSci Professor Deborah Ashby OBE FMedSci Sir Peter Lachmann FRS FMedSci Professor Dame Frances Ashcroft DBE Professor Leon Lagnado FMedSci FRS FMedSci Professor Anthony Barrett FRS FMedSci Professor Ajit Lalvani FMedSci Professor Gillian Bates FRS FMedSci Professor Deborah Lawlor CBE FMedSci Professor Facundo Batista FMedSci Professor Joy Lawn FMedSci Professor Stephan Beck FMedSci Professor Susan Lea FMedSci Professor Jill Belch OBE FMedSci Professor Sir Robert Lechler PMedSci Professor Sir John Bell GBE FRS Dr Melanie Lee CBE FMedSci HonFREng FMedSci Professor Wendy Bickmore FRS FRSE Professor Andrew Lees FMedSci FMedSci Professor Sir Adrian Bird CBE FRS FRSE Professor Stafford Lightman FRS FMedSci FMedSci Professor Ewan Birney CBE FRS Professor Janet Lord FMedSci FMedSci Professor Dorothy Bishop FRS FBA Professor Thomas MacDonald FMedSci FMedSci Professor Rona MacKie CBE FRSE Professor Jane Blazeby FMedSci Sir Stephen Bloom FRS FMedSci Professor Giovanna Mallucci FMedSci Sir Tom Blundell FRS FMedSci Dr Fiona Marshall FMedSci Professor Dame Theresa Marteau DBE Professor Peter -
Drugging the Undruggable: Advances on RAS Targeting in Cancer
G C A T T A C G G C A T genes Review Drugging the Undruggable: Advances on RAS Targeting in Cancer Miriam Molina-Arcas 1,*, Amit Samani 1,2,* and Julian Downward 1,3 1 Oncogene Biology Laboratory, Francis Crick Institute, London NW1 1AT, UK; [email protected] 2 Department of Medical Oncology, Imperial College Healthcare NHS Trust, London W2 1NY, UK 3 Lung Cancer Group, Institute of Cancer Research, London SW3 6JB, UK * Correspondence: [email protected] (M.M.-A.); [email protected] (A.S.) Abstract: Around 20% of all malignancies harbour activating mutations in RAS isoforms. Despite this, there is a deficiency of RAS-targeting agents licensed for therapeutic use. The picomolar affinity of RAS for GTP, and the lack of suitable pockets for high-affinity small-molecule binding, precluded effective therapies despite decades of research. Recently, characterisation of the biochemical properties of KRAS-G12C along with discovery of its ‘switch-II pocket’ have allowed development of effective mutant-specific inhibitors. Currently seven KRAS-G12C inhibitors are in clinical trials and sotorasib has become the first one to be granted FDA approval. Here, we discuss historical efforts to target RAS directly and approaches to target RAS effector signalling, including combinations that overcome limitations of single-agent targeting. We also review pre-clinical and clinical evidence for the efficacy of KRAS-G12C inhibitor monotherapy followed by an illustration of combination therapies designed to overcome primary resistance and extend durability of response. Finally, we briefly discuss novel approaches to targeting non-G12C mutant isoforms. -
Second RAS Initiative Symposium Sponsored by the National Cancer Institute Advanced Technology Research Facility, Frederick, MD December 6-8, 2017
The Second RAS Initiative Symposium Sponsored by the National Cancer Institute Advanced Technology Research Facility, Frederick, MD December 6-8, 2017 December 6 8:00 am – 8:15 am Welcome from the NCI Director Norman Sharpless 8:15 am – 9:00 am Keynote Frank McCormick (RAS Initiative, University of California, San Francisco) 9:00 am – 9:30 am Organoids as Model Systems for Tumorigenesis Calvin Kuo (Stanford University) 9:30 am – 9:50 am Break 9:50 am – 12:10 pm Activated RAS and Oncogenesis - Chair: Jeff Settleman Douglas Lowy (National Cancer Institute) Christopher Counter (Duke University) Matthew Vander Heiden (Massachusetts Institute of Technology) Marie Evangelista (Genentech) Aaron Hobbs (Der Lab, University of North Carolina, Chapel Hill) 12:10 pm – 1:10 pm Lunch on your own 1:10 pm – 3:15 pm Poster Session #1 3:15 pm – 4:15 pm RAS Multimers at the Membrane - Chair: John Hancock Yao-Cheng Li (Wahl Lab, Salk Institute) Margie Sutton (Bast Lab, MD Anderson) Chiara Ambrogio (Jänne Lab, Dana Farber Cancer Institute) 4:15 pm – 5:30 pm RAS Membrane Modeling and Dynamics - Chair: Dwight Nissley Roland Winter (Technische Universität Dortmund) Fred Streitz (Lawrence Livermore National Laboratory) Chris Neale (Garcia Lab, Los Alamos National Laboratory) Walkersville Social Hall 79 West Frederick Street, Walkersville 6:15 – 7:00 pm Hors d’oeuvres, cash bar 7:00 pm Dinner December 7 8:00 am – 10:00 am Tumor Dynamics - Chair: Rosalie Sears Dafna Bar-Sagi (New York University) David Tuveson (Cold Spring Harbor Laboratory) Channing Der (University -
Zusammenstellung Österreichischer Museen Mit Volkskundlichem Charakter 39-67 © Bundesministerium F
ZOBODAT - www.zobodat.at Zoologisch-Botanische Datenbank/Zoological-Botanical Database Digitale Literatur/Digital Literature Zeitschrift/Journal: Österreichs Museen stellen sich vor Jahr/Year: 1980 Band/Volume: 13 Autor(en)/Author(s): Gottschall Klaus Artikel/Article: Zusammenstellung österreichischer Museen mit volkskundlichem Charakter 39-67 © Bundesministerium f. Wissenschaft und Forschung; download unter www.zobodat.at Dr. Klaus Gottschall ZUSAMMENSTELLUNG ÖSTERREICHISCHER MUSEEN MIT VOLKSKUNDLICHEM CHARAKTER Die Liste der hier aufgeführten Museen beansprucht keine Vollständig keit. Die angeführten Daten wurden dankenswerter Weise von den ver schiedenen Landesmuseen zur Verfügung gestellt. Im wesentlichen spie gelt diese Liste den Stand Mai 1980. Lediglich vom Lande Niederöster reich konnten Daten nur ex 1973/1974 vermittelt werden. Auch das Land Kärnten mußte zeitbedingt umfangsmäßig Einschränkungen vornehmen. Ähnliches gilt für das Land bzw. die Stadt Wien; hier mußte eine Be schränkung insoferne vorgenommen werden, als nur die überregionalen bzw. Großmuseen aufgenommen wurden. Die zahlreichen, wichtigen Be zirksmuseen konnten nicht mehr erfaßt werden. Literaturhinweise: Rotraut ACKER-SUTTER: Heimatmuseen im Lande Salzburg. Selbstverlag des Salzburger Bildungswerkes, Salzburg 1980, 152 S. Gudrun B.-KLOSTER (Hg.); Handbuch der Museen. Deutschland BRD, DDR, Ö sterreich, Schweiz. Bd. 2: DDR, Österreich, Schweiz, Register. V er lag D okum entation, M ünchen-Pullach und Berlin 1971, XVI S., S. 643 bis 1300. österreichische FREMDENVERKEHRSWERBUNG (Hg.): Museen und Kunstdenkmäler in Österreich. Wien o. J., 88 S. Paul GNUVA: Museen in Europa. Wichtige und originelle Sammlungen. Kunst, Natur, Technik, Folklore, Hobby. RV Reise- und Verkehrsverlag GmbH., Berlin 1977, 296 S. Franz C. LIPP, Heidelinde DIMT: Schloßmuseum Linz. Führer durch die Sammlungen. Oberösterreichischer Landesverlag, Linz 1978, 192 S. Wolfgang MILAN (Bearb.): Museen und Sammlungen in Österreich. -
Landesmuseum Joanneum Graz Jahresbericht
©Digitalisierung Biologiezentrum Linz; download www.zobodat.at LANDESMUSEUM JOANNEUM GRAZ JAHRESBERICHT 1982 ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at 2 Abteilung für Mineralogie LandesmuseumJoanneum Raub© rgçisee 10 A-8010 Graz, AUSTRIA ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at LANDESMUSEUM JOANNEUM GRAZ, JAHRESBERICHT 1982 ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at LANDESMUSEUM JOANNEUM GRAZ JAHRESBERICHT 1982 NEUE FOLGE 12 - GRAZ 1983 ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at Nach den Berichten der Abteilungen redigiert von Eugen B r eg a n t und Dr. Detlef E rn et Graz 1983 Herausgegeben von der Direktion des Steiermärkischen Landesmuseums Joanneum, Raubergasse 10/1, A-8010 G raz Direktor: Dr. Friedrich W aidacher Gesamtherstellung: Buch- und Offsetdruckerei Styria, Judenburg Gesetzt aus Sabon — Berthold ©Digitalisierung Biologiezentrum Linz; download www.zobodat.at Inhalt Kuratorium 7 Bautätigkeit und Einrichtung 11 Sonderausstellungen 13 Veranstaltungen 19 Besuchsstatistik 1982 25 Verkäufliche Veröffentlichungen 27 Verkäufliche Diapositive und Bildpostkarten 33 Berichte Direktion 35 Referat für Jugendbetreuung 39 Abteilung für Geologie, Paläontologie und Bergbau 44 Abteilung für Mineralogie 51 Abteilung für Botanik 60 Abteilung für Zoologie 70 Abteilung für Vor- und Frühgeschichte und Münzensammlung 82 Abteilung für Kunstgewerbe 89 Landeszeughaus 95 Alte Galerie 101 Neue Galerie 105 Steirisches Volkskundemuseum 111 Außenstelle Stainz 116 Jagdmuseum 120 Abteilung Schloß Eggenberg 126 Landschaftsmuseum Schloß Trautenfels 134 Bild- und Tonarchiv 137 Beiträge K. R. Lorenz: Das geistige Erbe Erzherzog Johanns. Überlegungen zum Erzherzog-Johann-Gedenkjahr 145 F. Ebner: Erfahrungen mit der Wanderausstellung „Fossilien in der Steiermark — 500 Millionen Jahre Erdgeschichte“ 149 Z. -
№ Wca № Castles Prefix Name of Castle Oe-00001 Oe-30001
№ WCA № CASTLES PREFIX NAME OF CASTLE LOCATION INFORMATION OE-00001 OE-30001 OE3 BURGRUINE AGGSTEIN SCHONBUHEL-AGGSBACH, AGGSTEIN 48° 18' 52" N 15° 25' 18" O OE-00002 OE-20002 OE2 BURGRUINE WEYER BRAMBERG AM WILDKOGEL 47° 15' 38,8" N 12° 19' 4,7" O OE-00003 OE-40003 OE4 BURG BERNSTEIN BERNSTEIN, SCHLOSSWEG 1 47° 24' 23,5" N 16° 15' 7,1" O OE-00004 OE-40004 OE4 BURG FORCHTENSTEIN FORCHTENSTEIN, MELINDA-ESTERHAZY-PLATZ 1 47° 42' 34" N 16° 19' 51" O OE-00005 OE-40005 OE4 BURG GUSSING GUSSING, BATTHYANY-STRASSE 10 47° 3' 24,5" N 16° 19' 22,5" O OE-00006 OE-40006 OE4 BURGRUINE LANDSEE MARKT SANKT MARTIN, LANDSEE 47° 33' 50" N 16° 20' 54" O OE-00007 OE-40007 OE4 BURG LOCKENHAUS LOCKENHAUS, GUNSERSTRASSE 5 47° 24' 14,5" N 16° 25' 28,5" O OE-00008 OE-40008 OE4 BURG SCHLAINING STADTSCHLAINING 47° 19' 20" N 16° 16' 49" O OE-00009 OE-80009 OE8 BURGRUINE AICHELBURG ST. STEFAN IM GAILTAL, NIESELACH 46° 36' 38,6" N 13° 30' 45,6" O OE-00010 OE-80010 OE8 KLOSTERRUINE ARNOLDSTEIN ARNOLDSTEIN, KLOSTERWEG 3 46° 32' 55" N 13° 42' 34" O OE-00011 OE-80011 OE8 BURG DIETRICHSTEIN FELDKIRCHEN, DIETRICHSTEIN 46° 43' 34" N 14° 7' 45" O OE-00012 OE-80012 OE8 BURG FALKENSTEIN OBERVELLACH-PFAFFENBERG 46° 55' 20,4" N 13° 14' 24,6" E OE-00014 OE-80014 OE8 BURGRUINE FEDERAUN VILLACH, OBERFEDERAUN 46° 34' 12,6" N 13° 48' 34,5" E OE-00015 OE-80015 OE8 BURGRUINE FELDSBERG LURNFELD, ZUR FELDSBERG 46° 50' 28" N 13° 23' 42" E OE-00016 OE-80016 OE8 BURG FINKENSTEIN FINKENSTEIN, ALTFINKENSTEIN 13 46° 37' 47,7" N 13° 54' 11,1" E OE-00017 OE-80017 OE8 BURGRUINE FLASCHBERG OBERDRAUBURG, -
Combining Three Antibodies Nullifies Feedback-Mediated Resistance to Erlotinib in Lung Cancer
RESEARCH ARTICLE CANCER Combining three antibodies nullifies feedback-mediated resistance to erlotinib in lung cancer Maicol Mancini,1 Nadège Gaborit,1 Moshit Lindzen,1 Tomer Meir Salame,2 Massimiliano Dall’Ora,1 Michal Sevilla-Sharon,1 Ali Abdul-Hai,1,3 Julian Downward,4,5 Yosef Yarden1* Despite initial responses to targeted kinase inhibitors, lung cancer patients presenting with primary epidermal growth factor receptor (EGFR) mutations acquire resistance, often due to a second-site mutation (T790M). However, clinical trials found no survival benefits in patients treated with a monoclonal antibody (mAb) to EGFR that should block activation of the mutated receptor and thus bypass resistance to molecules that target the catalytic or ATP-binding site. Using cell lines with the T790M mutation, we discovered that pro- longed exposure to mAbs against only the EGFR triggered network rewiring by (i) stimulating the extra- Downloaded from cellular signal–regulated kinase (ERK) pathway; (ii) inducing the transcription of HER2 (human epidermal growth factor receptor 2) and HER3, which encode other members of the EGFR family, and the gene encoding HGF, which is the ligand for the receptor tyrosine kinase MET; and (iii) stimulating the interaction between MET and HER3, which promoted MET activity. Supplementing the EGFR-specific mAb with those targeting HER2 and HER3 suppressed these compensatory feedback loops in cultured lung cancer cells. The triple mAb com- bination targeting all three receptors prevented the activation of ERK, accelerated the degradation of the re- ceptors, inhibited the proliferation of tumor cells but not of normal cells, and markedly reduced the growth of http://stke.sciencemag.org/ tumors in mice xenografted with cells that were resistant to combined treatment with erlotinib and the single function-blocking EGFR mAb. -
Life Changing Science
LIFE CHANGING SCIENCE The Francis Crick Institute Annual Review 2017/18 AN INSTITUTE FOR DISCOVERY Our commitment to excellence, our emphasis on multidisciplinary research, our focus on young and emerging talent and our novel ways of partnership working are some of the factors that set the Crick apart. Front cover Vaccinia virus infection (green) disrupts a layer of epithelial cells (red/blue). Courtesy of Michael Way, Group Leader at the Crick. INTRODUCTION 2 Who we are Our year at a glance 2 Introduction by Paul Nurse 4 The Francis Crick Institute is a biomedical Progress against our strategy 6 discovery institute dedicated to understanding the RESEARCH HIGHLIGHTS 10 Cancer-causing mutation fundamental biology underlying health and disease. suppresses immune system 11 Our work is helping to build an understanding of Predicting lung cancer’s return 12 New understanding of human why disease develops and to translate discoveries embryo development 14 Chemical attraction could improve into new ways to prevent, diagnose and treat cancer immunotherapy 16 illnesses such as cancer, heart disease, stroke, Genes linked to malaria parasites’ persistence 17 infections and neurodegenerative diseases. Architecture of our ‘second brain’ 18 Cause of infertility side-stepped in mice 19 Mechanism for spinal cord development discovered 20 A new layer of complexity in embryo development 21 Two DNAs wedded with this ring 22 Unravelling how DNA gets copied 23 Telomerase’s dark side discovered 24 REVIEW OF THE YEAR 26 New group leaders arrive 27 Joined-up thinking 30 Focusing on the molecules of life 32 CryoEM at the Crick 34 Bringing academia and industry closer together 36 The people making research happen 38 Patterns in art and science 40 Rewarding research 42 Appointments 43 Supporting new discoveries 44 Our vision What’s inside Our vision is to be a world- We bring together outstanding scientists Science feature 32 leading multidisciplinary from all disciplines and carry out research Sophisticated microscopy is being biomedical research institute.